Use of azithromycin and death from cardiovascular causes

N Engl J Med. 2013 May 2;368(18):1704-12. doi: 10.1056/NEJMoa1300799.


Background: Azithromycin use is associated with an increased risk of death from cardiovascular causes among patients at high baseline risk. Whether azithromycin confers a similar risk in the unselected general population is unknown.

Methods: We conducted a nationwide historical cohort study involving Danish adults (18 to 64 years of age), linking registry data on filled prescriptions, causes of death, and patient characteristics for the period from 1997 through 2010. We estimated rate ratios for death from cardiovascular causes, comparing 1,102,050 episodes of azithromycin use with no use of antibiotic agents (matched in a 1:1 ratio according to propensity score, for a total of 2,204,100 episodes) and comparing 1,102,419 episodes of azithromycin use with 7,364,292 episodes of penicillin V use (an antibiotic with similar indications; analysis was conducted with adjustment for propensity score).

Results: The risk of death from cardiovascular causes was significantly increased with current use of azithromycin (defined as a 5-day treatment episode), as compared with no use of antibiotics (rate ratio, 2.85; 95% confidence interval [CI], 1.13 to 7.24). The analysis relative to an antibiotic comparator included 17 deaths from cardiovascular causes during current azithromycin use (crude rate, 1.1 per 1000 person-years) and 146 during current penicillin V use (crude rate, 1.5 per 1000 person-years). With adjustment for propensity scores, current azithromycin use was not associated with an increased risk of cardiovascular death, as compared with penicillin V (rate ratio, 0.93; 95% CI, 0.56 to 1.55). The adjusted absolute risk difference for current use of azithromycin, as compared with penicillin V, was -1 cardiovascular death (95% CI, -9 to 11) per 1 million treatment episodes.

Conclusions: Azithromycin use was not associated with an increased risk of death from cardiovascular causes in a general population of young and middle-aged adults. (Funded by the Danish Medical Research Council.).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Azithromycin / adverse effects*
  • Azithromycin / therapeutic use
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / mortality*
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Humans
  • Infections / complications
  • Infections / drug therapy
  • Male
  • Middle Aged
  • Penicillin V / adverse effects*
  • Penicillin V / therapeutic use
  • Propensity Score
  • Registries
  • Risk
  • Young Adult


  • Anti-Bacterial Agents
  • Azithromycin
  • Penicillin V